Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, Australia ; The Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Melbourne, Australia.
PLoS One. 2013 Sep 9;8(9):e73505. doi: 10.1371/journal.pone.0073505. eCollection 2013.
The mechanisms by which valproate, one of the most widely prescribed anti-epileptic drugs, suppresses seizures have not been fully elucidated but may involve up-regulation of neuropeptide Y (NPY). We investigated the effects of valproate treatment in Genetic Absence Epilepsy Rats from Strasbourg (GAERS) on brain NPY mRNA expression and seizure control. GAERS were administered either valproate (42 mg.kg(-1) hr(-1)) or saline continuously for 5 days. Electroencephalograms were recorded for 24 hrs on treatment days 1, 3 and 5 and the percentage of time spent in seizure activity was analysed. NPY mRNA expression was measured in different brain regions using qPCR. Valproate treatment suppressed seizures by 80% in GAERS (p<0.05) and increased NPY mRNA expression in the thalamus (p<0.05) compared to saline treatment. These results demonstrate that long-term valproate treatment results in an upregulation of thalamic expression of NPY implicating this as a potential contributor to the mechanism by which valproate suppresses absence seizures.
丙戊酸钠是最广泛应用的抗癫痫药物之一，其抑制癫痫发作的机制尚未完全阐明，但可能涉及神经肽 Y（NPY）的上调。我们研究了丙戊酸钠治疗 Strasbourg 遗传性癫痫大鼠（GAERS）对脑 NPY mRNA 表达和癫痫控制的影响。GAERS 连续 5 天给予丙戊酸钠（42mg.kg(-1)hr(-1))或生理盐水。在治疗第 1、3 和 5 天记录 24 小时脑电图，并分析癫痫发作时间百分比。使用 qPCR 测量不同脑区的 NPY mRNA 表达。丙戊酸钠治疗使 GAERS 的癫痫发作抑制了 80%（p<0.05），并使丘脑 NPY mRNA 表达增加（p<0.05），与生理盐水治疗相比。这些结果表明，长期丙戊酸钠治疗导致丘脑 NPY 表达上调，这可能是丙戊酸钠抑制失神发作的机制之一。
